Characterization of a Mouse Model of Cancer Related Fatigue using a Physical Activity Test Battery

Of the myriad of symptoms associated with cancer the most commonly reported is fatigue; it is thought to affect more than 70% of cancer patients and even a higher percentage (80-99%) of patients who are currently undergoing treatment. Cancer related fatigue (CRF) is a multidimensional event arising from the complex interplay of physical, mental, emotional, environmental, physiological, and pathological factors. Currently there are no available treatment options for CRF, which is not surprising given the lack of animal models to study this complex phenomenon. PURPOSE: The purpose of this study was to characterize the APCMin/+ mouse as a model to study CRF using five distinct modes of physical activity. METHODS: Wildtype and APCMin/+ mice were randomly assigned to groups according to age (6, 10, 14, or 18wk) with separate mice used at each time-point. Physical activity measures including, voluntary wheel running, treadmill running performance, open field activity, rotorod performance and grip strength were determined at each time-point. RESULTS: Voluntary wheel-running activity (distance, time on the wheel, and peak speed), a measure of willingness to be active, was significantly decreased in APCMin/+ mice at 10, 14 and 18wks of age (P<0.05), but not at 6 wks. Treadmill running performance, an indicator of endurance capacity, was decreased in APCMin/+ mice at 14 and 18 wks (P<0.05), but not at 6 or 10wks. At 18wks APCMin/+ mice exhibited significantly less open field activity (emotionality) than wildtype mice (P<0.05), and there was a trend toward a decrease at 10 and 14wks. There was no significant decreases in grip strength and rotorod performance, measures of muscle strength and neuromuscular coordination, respectively, in APCMin/+ mice over time. CONCLUSIONS: These findings suggest that voluntary wheel-running activity is the most sensitive physical activity measure of CRF followed by treadmill running and open field activity. Muscular strength and coordination are not affected in this model of CRF. Overall these data provide strong support for further development of the APCMin/+ mouse to study the mechanisms of CRF as well as therapeutic strategies to delay or prevent its occurrence.